NEUROCHEMICAL ALTERATIONS BY DESIGNER DRUGS

滥用3，4-亚甲二氧基甲基安非他明（MDMA）或摇头丸， 继续增加，特别是在大学校园。期间 在前一个资助期，我们和其他人研究了神经化学物质 在一次大剂量或重复较小剂量的 摇头丸色氨酸羟化酶（TPH）活性和 5-羟色胺及其代谢产物5-羟吲哚乙酸 （5 HIAA），已经在几个大脑区域观察到;这些变化在 肾上腺素能参数持续很长一段时间后， 停药 在目前的提案中，摇头丸及其 将对造成其影响的同系物进行调查。 可能发挥的作用 兴奋性氨基酸在MDMA诱导的效应中的作用将是 测定多巴胺（DA）和/或GHT是否参与MDMA- 诱导效应将通过以前在 我们对甲基苯丙胺及其类似物的调查;在这一部分， 这项研究将确定MDMA诱导的大脑变化， 神经肽浓度氧化应激的重要性和 将探讨肾上腺类固醇在反应中的可能作用。的 此外，亦会研究对二亚甲基双氧安非他明及其同类药物的耐受性发展。 最后，4-methylaminorex（UrEA），一种类似物， 最近在街上出现的，将被调查。 这些研究不仅将提供关于神经化学物质的信息， 滥用摇头丸和类似的设计药物的影响，但 多巴胺能、多巴胺能和 还将研究神经肽系统。

The abuse of 3,4-methylenedioxymethamphetamine (MDMA), or ecstasy, continues to increase, especially on college campuses. During the previous grant period we an others have investigated the neurochemical alterations that occur after one large or repeated smaller doses of MDMA. Profound decreases in tryptophan hydroxylase (TPH) activity and in 5-hydroxytryptamine (5HT) and its metabolite, 5-hydroxyindoleacetic acid (5HIAA), have been observed in several brain regions; these changes in serotonergic parameters persist for long periods of time after discontinuning the drug. In the current proposal, the mechanisms(s) by which MDMA and its congeners cause their effects will be investigated. The possible role of excitatory amino acids in the MDMA-induced effects will be determined. Whether dopamine (DA) and/or GHT are involved in the MDMA- induced effects will be assessed by techniques previously employed in our investigation of methamphetamine and its analogs; in this part of the study we will determine the MDMA-induced changes in brain neuropeptide concentrations. The importance of oxidative stress and the possible role of adrenal steroids in the response will be explored. The development of tolerance to MDMA and its congeners will also be studied. Finally, the neurochemical effects of 4-methylaminorex (UrEA), an analog that has recently appeared on the street, will be investigated. Not only will these studies provide information on the neurochemical effects of abuse of MDMA and similar designer drugs, but the interrelationship between the dopaminergic, serotonergic and neuropeptide systems will also be investigated.